RELA Gene: NF-κB p65 Subunit – Function, Expression, and Disease Relevance
Comprehensive biomedical overview of the RELA gene, encoding the p65 subunit of NF-κB, including genomic context, tissue expression, mutations, and clinical significance.
Gene Information Card
| Symbol | RELA |
|---|---|
| Full Name | RELA proto-oncogene, NF-kB subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 5970 ncbi.nlm.nih.gov/gene/5970 |
| Ensembl ID | ENSG00000173039 |
| UniProt ID | Q04206 |
| OMIM ID | 164011 |
| HGNC ID | 9955 |
| Aliases | NFKB3, p65, CMCU, NF-kB p65, nuclear factor NF-kappa-B p65 subunit |
Description
RELA (RELA proto-oncogene, NF-kB subunit) encodes the p65 subunit of the NF-κB transcription factor complex. This protein is a central component of the canonical NF-κB signaling pathway, which regulates genes involved in inflammation, immunity, cell survival, proliferation, and apoptosis. RELA is constitutively expressed in most tissues but is activated in response to various stimuli including cytokines, pathogens, and stress signals. It functions as a transcriptional activator when bound to DNA as a homodimer or heterodimer with other NF-κB family members. Dysregulation of RELA is implicated in chronic inflammation, autoimmune diseases, and multiple cancer types.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) | Constitutive activation of NF-κB via RELA leads to sustained expression of pro-inflammatory cytokines (TNF, IL-6, IL-1β) and chemokines, driving tissue inflammation and damage. | OMIM 164011; multiple GWAS and functional studies |
| Various cancers (breast, colon, lung, lymphoma) | RELA overexpression or constitutive nuclear localization promotes cell proliferation, survival, and metastasis by upregulating anti-apoptotic genes (BCL2, BIRC3) and cell cycle regulators (CCND1, MYC). | COSMIC; numerous cancer genomics studies |
| Incontinentia pigmenti (rare, germline loss-of-function) | Loss-of-function mutations in RELA impair NF-κB signaling, leading to ectodermal defects and immune dysfunction. | OMIM 164011; ClinVar |
| Autoimmune disorders (e.g., systemic lupus erythematosus) | Altered RELA activity affects regulatory T-cell function and promotes autoantibody production. | OMIM 164011; functional studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.8 | High |
| Spleen | 11.5 | High |
| Bone marrow | 10.2 | High |
| Lung | 8.4 | Medium |
| Liver | 7.1 | Medium |
| Brain | 5.3 | Low |
| Muscle | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.2 | High expression; constitutive NF-κB activity |
| K-562 (leukemia) | 12.7 | High expression; involved in leukemogenesis |
| A549 (lung cancer) | 9.8 | Medium-high; activated by inflammatory stimuli |
| MCF7 (breast cancer) | 8.1 | Medium; hormone-responsive regulation |
| HepG2 (liver cancer) | 6.5 | Medium; baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gln136* (Q136X) | Nonsense | Rare (<0.1%) | Truncated protein; loss of DNA-binding domain; loss-of-function |
| p.Arg246Trp (R246W) | Missense | 0.2% (COSMIC) | Altered DNA-binding affinity; potential gain-of-function in some contexts |
| p.Ser276Ala (S276A) | Missense | Experimental | Phosphorylation site loss; reduced transcriptional activity |
| p.Ser536Ala (S536A) | Missense | Experimental | Phosphorylation site loss; impaired nuclear translocation |
| Amplification (11q13.1) | Copy number gain | 5-10% in solid tumors | Increased RELA expression; enhanced NF-κB signaling |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift mutations leading to truncated p65 protein lacking the C-terminal transactivation domain, resulting in impaired NF-κB transcriptional activity and defective immune responses.
Gain of Function (GOF)
Missense mutations or gene amplification that enhance RELA stability, nuclear localization, or DNA-binding affinity, leading to constitutive NF-κB activation and oncogenic signaling.
Dominant Negative (DN)
Certain mutations (e.g., in the dimerization domain) produce p65 proteins that bind to other NF-κB subunits but fail to activate transcription, thereby suppressing wild-type NF-κB function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978) |
| • protein dimerization activity (GO:0046983) | • NF-kappaB binding (GO:0035976) |
| • chromatin binding (GO:0003682) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • signal transduction (GO:0007165) |
| • inflammatory response (GO:0006954) | • apoptotic process (GO:0006915) |
Pathways
• NF-kappaB signaling pathway (KEGG hsa04064)
• Toll-like receptor signaling pathway (KEGG hsa04620)
• TNF signaling pathway (KEGG hsa04668)
• B cell receptor signaling pathway (KEGG hsa04662)
• T cell receptor signaling pathway (KEGG hsa04660)
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• Apoptosis (KEGG hsa04210)
Protein Summary
The RELA protein (p65) is a 551-amino acid transcription factor containing an N-terminal Rel homology domain (RHD) responsible for DNA binding and dimerization, and a C-terminal transactivation domain (TAD) that recruits coactivators. It forms homo- or heterodimers with other NF-κB family members (e.g., p50/p105, c-Rel, RelB) and is sequestered in the cytoplasm by IκB inhibitors. Upon stimulation, IκB is phosphorylated and degraded, allowing RELA to translocate to the nucleus and activate target gene transcription. Post-translational modifications, including phosphorylation at Ser276 and Ser536, acetylation, and ubiquitination, regulate its activity and stability. RELA is essential for normal immune function and is a key therapeutic target in inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RELA Knockout HEK293 Cell Line | EDJ-KQ588 | Human | 5970 | Details Get a Quote |
| RELA Knockout A-549 Cell Line | EDJ-KQ19008 | Human | 5970 | Details Get a Quote |
| RELA Knockout HCT 116 Cell Line | EDJ-KQ19009 | Human | 5970 | Details Get a Quote |
| RELA Knockout HeLa Cell Line | EDJ-KQ19010 | Human | 5970 | Details Get a Quote |
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